The Journal of Experimental Medicine
Track the topics, authors and articles important to you
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 6 September 2005. doi:10.1084/jem.20050607
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 5, 663-671
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 2186K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Filippov, S.
Right arrow Articles by Weiss, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Filippov, S.
Right arrow Articles by Weiss, S. J.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Substance via MeSH
Medline Plus Health Information
*Vascular Diseases
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells

Sergey Filippov1, Gerald C. Koenig2, Tae-Hwa Chun1, Kevin B. Hotary1, Ichiro Ota1, Thomas H. Bugge3, Joseph D. Roberts2, William P. Fay2, Henning Birkedal-Hansen4, Kenn Holmbeck4, Farideh Sabeh1, Edward D. Allen1, and Stephen J. Weiss1

1 Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109
2 Division of Cardiology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109
3 Protease and Tissue Remodeling Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892
4 Matrix Metalloproteinase Unit, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892

CORRESPONDENCE Stephen J. Weiss: sjweiss{at}umich.edu

During pathologic vessel remodeling, vascular smooth muscle cells (VSMCs) embedded within the collagen-rich matrix of the artery wall mobilize uncharacterized proteolytic systems to infiltrate the subendothelial space and generate neointimal lesions. Although the VSMC-derived serine proteinases, plasminogen activator and plasminogen, the cysteine proteinases, cathepsins L, S, and K, and the matrix metalloproteinases MMP-2 and MMP-9 have each been linked to pathologic matrix-remodeling states in vitro and in vivo, the role that these or other proteinases play in allowing VSMCs to negotiate the three-dimensional (3-D) cross-linked extracellular matrix of the arterial wall remains undefined. Herein, we demonstrate that VSMCs proteolytically remodel and invade collagenous barriers independently of plasmin, cathepsins L, S, or K, MMP-2, or MMP-9. Instead, we identify the membrane-anchored matrix metalloproteinase, MT1-MMP, as the key pericellular collagenolysin that controls the ability of VSMCs to degrade and infiltrate 3-D barriers of interstitial collagen, including the arterial wall. Furthermore, genetic deletion of the proteinase affords mice with a protected status against neointimal hyperplasia and lumen narrowing in vivo. These studies suggest that therapeutic interventions designed to target MT1-MMP could prove beneficial in a range of human vascular disease states associated with the destructive remodeling of the vessel wall extracellular matrix.

Abbreviations used: 2-D, two-dimensional; 3-D, three- dimensional; BrdU, bromodeoxyuridine; FGF, fibroblast growth factor; MMP, matrix metalloproteinase; MT1, membrane type I; PCNA, proliferating cell nuclear antigen; PDGF, platelet-derived growth factor; TIMP, tissue inhibitor of metalloproteinases; VSMC, vascular smooth muscle cell.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS